Bis(dicholroacetyl)diamine-induced Craniofacial Anomalies in Jcl: ICR and A/J Mice

Abstract Craniofacial anomalies induced by bis(dichloroacetyl)diamine (bisdiamine) were studied in two strains of mice, Jcl:ICR and A/J. Bisdiamine was given by oral intubation at a dose of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of pregnancy (VP = day 0). A/J was more susceptible to embryolethal effects of bisdiamine and had a longer sensitive period to teratogenic effects of bisdiamine. The most susceptible period for craniofacial anomalies induced by bisdiamine in A/J was one day later than that in Jcl:ICR. In both strains, median facial anomalies, cleft palate, protuberance(s) on the forehead and open eyelids were commonly induced craniofacial anomalies. Median facial anomalies were more frequent and also more severe in Jcl:ICR, while lateral cleft lip was observed only in A/J.
Strain differences for embryolethality and types and frequencies of craniofacial anomalies are discussed on the basis of genetic homozygosity, craniofacial development and embryonic face shape immediately before the fusion of the nasal prominences. Neural crest cells are thought to be the target of bisdiamine.     

Long-Term Clinical Follow-up after Sirolimus-Eluting Stent versus Bare Metal Stent Implantation in Patients with Acute Coronary Syndrome

Background and Objective: Drug-eluting stents have been shown to reduce the incidence of restenosis and target vessel revascularization (TVR) compared with bare metal stents (BMSs); however, the long-term efficacy of sirolimus-eluting stent (SES) implantation in patients with acute coronary syndrome (ACS) has not been well established. We have investigated the long-term clinical outcome of SES in patients with ACS.
Methods: Consecutive 245 patients with ACS treated by primary stenting within 24 hours after onset were enrolled. There were 128 patients treated with SES and 117 patients were treated with BMS. We evaluated the incidence of major cardiac events (MACE; total death, nonfatal myocardial infarction, TVR) at 3 years, comparing with 8-month clinical outcome.
Results: Eight-month clinical follow-up shows a significantly lower incidence of TVR in the SES group, 3.1% in the SES group versus 9.4% in the BMS group (P = 0.04). At 3-year clinical follow-up, there was no significant difference in the rate of TVR between the two groups, 8.4% versus 12.4% (P = 0.37). Cumulative incidence of total MACE was 9.2% in the SES group compared with 15.9% in the BMS group (P = 0.18). Only one case of stent thrombosis was observed in the SES (late thrombosis), while two cases of stent thrombosis occurred in the BMS group (late and very late thrombosis; P = 0.55).
Conclusion: SES implantation in patients with ACS is associated with favorable long-term clinical outcome with no excess of late stent thrombosis. Further long-term clinical follow-up will be warranted to confirm the safety and efficacy of SES.     

Induction of Suppressor Cell Activity by Human Pregnancy Serum

ABSTRACT: Third trimester pregnancy serum caused a dose-dependent inhibition of the one-way allogeneic mixed leukocyte reaction (MLR) through an effect that occurred during the first 48 hours of culture. Pregnancy serum also inhibited the mitogenic responsiveness of normal mononuclear leukocytes to concanavalin A (Con A) while the responses to phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were less affected. Preincubation of normal peripheral blood mononuclear cells (PBMC) for 48 hours with 10% pregnancy serum enhanced a suppressor activity transferable with cells. These pregnancy serum-induced effector cells suppressed the MLR only when they were autologous to the responder population (p < 0.05). The same suppressor cell preparation inhibited the proliferative responses of autologous PBMC to Con A (p < 0.001) and PWM (p < 0.05). These data suggest that one or more factors in pregnancy serum can induce or enhance suppressor cell activity in vitro. A comparable increase in suppressor cell activity in vivo may be responsible for blocking maternal rejection of the fetus and for the observed improvement in clinical activity of rheumatoid arthritis during pregnancy.     

APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis

Currant histopathoiogical evidence suggests that gall-bladder cancer has two main morphological pathways for Its development: de novo ( ab Inltlo ) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested porymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunoriisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of Invasion, but not in 16 tumors of carcinoma-ln-pyloric-gland-type adenoma, or In 51 adenomas (47 pyloric gland-type and 4 Intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, ail four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carclnoma-in-pylortc-gland-type adenoma develops from p53 -, K-ras -, and APC -gene-unrelated, as yet unknown, alteration.     

Extensive intraductal component (EIC) and estrogen receptor (ER) status in breast cancer

The extensive intraductal component (EIC) of primary breast carcinoma is a special spread pattern observed In the breast. Extensive intradwtal component may extend diffusely over the entim breast. Therefore, EIC Is considered to be an important risk factor for local recurrence in breast-conserving therapy. However, the pathogenesis of EIC remains uncertain. Whether or not the estrogen receptor (ER) has an influence on its biologic behavior has not been fully studied. A consecutive series of 142 breast carcinomas submitted to the pathology department were examined on step gross dons of 5.0 mm thick. Extensive intraductal component was determined and divided into three types. Estrogen receptor was examined using both immunohistochemistry (ER-IHC) and enzyme immunoassay (ER-EIA). Extensive intraductal component was found In 78 of 138 (56.52%) invaslve carcinomas including invasive ductal carcinoma with a predominant intraductal component. Estrogen receptor-IHC positivity was 42.96% (61/142) in the Invasive breast carcinoma. Estrogen receptor positivity showed no significant difference between ElC-positive and -negative cases, as well as between EIC and Invasive main tumor in the ElC-positive cases. But within the ElC-positive group, ER positivity was found to be higher in the peripheral type of ElC-II and ElC-III than in the central type of ElC-I ( P <0.05). Although ER may not play an essential role in the pathogenesis of EIC, it has shown some significance in the development of peripheral type EIC because of its higher presence in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I.     

Genetic polymorphism of coagulation factor XIIIB subunit in Japanese

Genetic polymorphism of coagulation factor XIIIB subunit in Japanese has been described, using thin-layer agarose gel isoelectric focusing followed by immunofixation.
Phenotypes of factor XIIIB subunit were essentially classified into three common patterns A, B and AB. It is estimated that the phenotypes are determined by two codominant alleles. A new rare variant B' has been detected in Japanese.
Gene frequencies calculated from 304 individuals showed FXIII-B^A =0.735, FXIII-B^B = 0.252 and FXIII-B^B' = 0.013, respectively. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium.     

CASE REPORT; Haemangioma of the small intestine complicated by protein-losing gastroenteropathy

We report a case of haemangioma of the small intestine complicated by protein-losing gastroenteropathy. A 32-year-old female had suffered from hypoproteinaemia for 6 years, but the cause of this condition had not been determined. On diagnosis and therapy for hypoproteinaemia, intra-operative endoscopy and histological examination were performed and she was subsequently diagnosed with capillary haemangioma of the small intestine. Angiography was not useful for the detection of capillary haemangioma of the small intestine in this case. Although intestinal haemangioma is an important cause of gastrointestinal bleeding, protein loss is an extremely rare complication and this case is the first to be reported in Japan.